Main active components of Jiawei Gegen Qinlian decoction protects against ulcerative colitis under different dietary environments in a gut microbiota-dependent manner
Main active components of Jiawei Gegen Qinlian decoction protects against ulcerative colitis under different dietary environments in a gut microbiota-dependent manner
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DOI：
10.1016/j.phrs.2021.105694
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发表时间：
2021-06-17
影响因子：
9.3
通讯作者：
Si, Hongbin
中科院分区：
文献类型：
--
作者：
Li, Qinmei;Cui, Yao;Si, Hongbin
葛根芩连汤作为治疗急性肠炎腹泻的有效药物，已有2000多年的历史。然而，GQD保护肠屏障免受溃疡性结肠炎（UC）的潜在分子机制仍不清楚。肠道菌群作为结肠内稳态的重要组成部分，与周围环境的动态演变和饮食结构的调整密切相关。目前，加味葛根芩连汤在不同饮食环境下对UC的疗效及作用机制尚不清楚。本研究选择加味葛根芩连汤的主要活性成分，构建合理有效的复方方案。分别采用“5%葡聚糖硫酸钠（DSS）”和“高温高湿+高糖高脂+酒精+5%DSS”诱导普通环境UC大鼠模型和岭南地区UC大鼠模型。然后，我们观察了PBM（89.96 mg/kg和179.92 mg/kg）对两种UC大鼠的治疗作用。通过肠道植物群消耗和粪便微生物群移植（FMT）实验来确定肠道微生物群在PBM抗UC作用中的作用。随后，我们分别用16 SrDNA技术和靶向代谢组学监测大鼠结肠肠道菌群和粪便代谢的变化。PBM处理的和FMT处理的大鼠的结肠炎症均显示出显著缓解，如通过体重减轻、血便、腹泻、疾病活动指数（DAI）评分、结肠长度缩短以及结肠组织学损伤减少所证明的。有趣的是，肠道植物群的消耗消除了PBM的保护作用，证实了肠道植物群在PBM的抗UC作用中的重要性。因此，我们的研究结果表明，PBM不仅可以通过增加阿克曼氏菌和罗姆布氏菌来调节肠道菌群，还可以减少肠道志贺菌。更重要的是，PBM可以增加结肠炎大鼠丙酸和总短链脂肪酸（SCFAs）的产生，调节中长链脂肪酸（M-LCFAs），维持胆汁酸（BAs）的稳态，调节氨基酸（AAs）代谢。肠内环境的改变可能与结肠黏膜抗炎、抗氧化及紧密连接蛋白表达上调有关。综上所述，PBM通过肠道微生物群依赖性显示出抗UC活性的潜力，并有望成为一种补充和替代药物草药疗法。
As an effective drug against acute enteritis diarrhea, Gegen Qinlian decoction (GQD) has a history of 2000 years. However, the potential molecular mechanism through which GQD could protect intestinal barrier from ulcerative colitis (UC) still remains undefined. As an important part of the homeostasis of the colon, gut microbiota is closely related to the dynamic evolution of the surrounding environment and the adjustment of dietary structure. At present, the effectiveness and mechanism of Jiawei Gegen Qinlian decoction against UC in different dietary environments are not clear. Here, the main active components of Jiawei Gegen Qinlian Decoction (PBM), were selected to construct a reasonable and effective compound scheme. We adopted "5% dextran sulfate sodium (DSS)" and "high temperature and humidity + high sugar and high fat + alcohol + 5%DSS" to induce UC rat models in general environment and UC rat models in Lingnan area, respectively. Then, we examined the therapeutic effects of PBM (89.96 mg/kg and 179.92 mg/kg) on two kinds of UC rats. The role of gut microbiota in the anti-UC effect of PBM was identified by intestinal flora consumption and fecal microbiota transplantation (FMT) experiments. Subsequently, we monitored the alterations of gut microbiota and fecal metabolism in the rat colon by 16Sr DNA technique and targeted metabonomics, respectively. The colon inflammation of the PBM-treated and the FMT-treated rats both showed significant relief, as evidenced by a reduction in body weight loss, bloody stool, diarrhea, disease activity index (DAI) score, shortening of colon length as well as decreased colon histology damage. Interestingly enough, the depletion of intestinal flora took away the protective effect of PBM, confirming the importance of intestinal flora in the anti-UC effect of PBM. Then our findings suggested that PBM could not only regulate the gut microbiota by increasing Akkermansia and Romboutsia but also decrease Escherichia-Shigella. More importantly, PBM could increase the production of propionate and total short-chain fatty acids (SCFAs) in colitis rats, regulate medium and long chain fatty acids (M-LCFAs), maintain bile acids (BAs) homeostasis, and regulate amino acids (AAs) metabolism. The transformation of intestinal environment might be related to the upregulation of anti-inflammation, anti-oxidation and tight junction protein expression in colonic mucosa. In summary, PBM showed potential for anti-UC activity through gut microbiota dependence and was expected to be a complementary and alternative medicine herb therapy.